Visceroendocrine responses elicited by neuropeptide Y in the nucleus tractus solitarius

Abstract

Neuropeptide Y (NPY) has been shown to be localized in a number of CNS regions, including the nucleus tractus solitarius (NTS). In this meeting report, a brief overview is presented of recent studies from our laboratory examining the role of NPY in NTS-mediated mechanisms of cardiorespiratory and Visceroendocrine regulation. Microinjections of NPY, NPY analogs, or C-terminal NPY fragments were made into the subpostremal NTS of anesthetized spontaneously breathing rats. NPY elicited pronounced dose-related depressor responses, bradycardia, and reductions in respiratory minute volume. The overall cardiorespiratory response pattern elicited by NPY was mimicked by NPY 13/23;6, a fragment of NPY exhibiting selective agonist properties at presynaptic Y 2 receptors, whereas the y 1 receptor-selective analog, [Leu 31,Pro 34]NPY, and the C-terminal inactive fragment, NPY 26–36, were found to be ineffective. In an effort to further characterize intrinsic NTS mechanisms mediating the NPY-evoked response pattern, NPY microinjections were similarly made in a group of rats with bilateral glossopharyngeovagotomy (G-vagotomy) and in a group of rats decerebrated at the supracollicular level. The results showed that whereas decerebration did not appreciably affect the NTS-mediated cardiorespiratory responses elicited by NPY. G-vagotomy enhanced the NPY-evoked hypotension while at the same time abolishing the NPY-evoked bradycardia and reductions in tidal volume. Taken together, these observations with G-vagotomized animals, along with the results from microinjection studies using selective ligands for NPY receptors, suggest that NPY may modulate primary visceral afferent information via activation of Y 2 receptors distributed at presynaptic sites in the subpostremal NTS. On the other hand, the influence of reciprocal NPY-containing neuronal connections with rostral brain regions on NTS-mediated cardiorespiratory responses elicited by NPY appeared not to be consequential, at least in normal rats. However, when similar microinjections of NPY were made into the same subpostremal NTS sites of intact rats which were diabetic, there was a dramatic attenuation in cardiorespiratory responsiveness to NPY. These results suggest that NPY-sensitive mechanisms in the NTS mediating cardiorespiratory responses may conceivably be influenced by the increased hypothalamic NPYergic activity that has been observed in diabetic rats. These observations, together with recent findings from our laboratory showing that microinjection of NPY into the same subpostremal NTS sites potently stimulates insulin secretion, provide support for the notion that NPY may play a crucial modulatory role in NTS-mediated Visceroendocrine response patterns involved in cardiorespiratory control and nutrient homeostasis.